Nipah virus is a member of the Paramyxoviridae family and is related to the Hendra virus (formerly called equine morbillivirus). The Nipah virus was initially isolated in 1999 upon examining samples from an outbreak of encephalitis and respiratory illness among adult men in Malaysia and Singapore (see, e.g., Chua et al., Lancet. 1999 Oct. 9; 354(9186):1257-9 and Paton et al., Lancet. 1999 Oct. 9; 354(9186):1253-6). The host for Nipah virus is still unknown, but flying foxes (bats of the Pteropus genus) are suspected to be the natural host.
Because of changes in ecological conditions, flying foxes are increasingly coming into contact with humans and domesticated animals. Therefore, it is conceivable that the viruses in flying foxes may infect domesticated animals and humans, which could result in a more virulent, possibly fatal, disease. Nipah virus caused a relatively mild disease in pigs in Malaysia and Singapore and the virus was transmitted to humans, cats and dogs through close contact with infected pigs.
Infectious with Nipah virus in humans has been associated with an encephalitis characterized by fever and drowsiness and more serious central nervous system disease, such as coma, seizures and inability to maintain breathing (see, e.g., Lee et al., Ann Neurol. 1999 September; 46(3):428-32). Illness with Nipah virus begins with 3-14 days of fever and headache, followed by drowsiness and disorientation characterized by mental confusion. These signs and symptoms can progress to coma within 24-48 hours. Some patients have had a respiratory illness during the early part of their infections. Serious nervous disease with Nipah virus encephalitis has been marked by some sequelae, such as persistent convulsions and personality changes. During the Nipah virus disease outbreak in 1998-1999, about 40% of the patients with serious nervous disease who entered hospitals died from the illness (see, e.g., Lam & Chua, Clin Infect Dis. 2002 May 1; 34 Suppl 2:S48-51).
Accordingly, a goal of animal health is the betterment of human health by preventing disease transmission between animals and/or humans.
Nipah virus infection can be prevented by avoiding animals that are known to be infected and using appropriate personal protective equipment devices when it is necessary to come into contact with potentially infected animals. The drug ribavirin has been shown to be effective against the Nipah virus in vitro, however, controlled drug investigations have not been performed and the clinical usefulness is uncertain.
If an efficient program to prevent or treat Nipah virus infection is to be developed, it will be necessary to define the viral antigens which are important in inducing protective responses and to formulate potential immunoprophylactic treatments. The attachment (G) and fusion (F) glycoproteins of Nipah virus have been implicated as viral antigens (see, e.g., Bossart et al., J. Virol. 2002 November; 76(22):11186-98 and Guillaume et al., J. Virol. 2004 January; 78(2):834-40). The Nipah virus glycoproteins (G and F) when expressed as vaccinia virus recombinants have induced an immune response in hamsters which protected against a lethal challenge by Nipah virus (see, e.g., Guillaume et al., J. Virol. 2004 January; 78(2):834-40). However, it was observed that in both active and passive immunization, the antibody response to Nipah virus was strongly stimulated, suggesting that the efficacy of the immunization is related to the capability of the vector to replicate.
Accordingly, there is a need in the art for an efficacious and reliable Nipah virus vaccine where heterologous proteins are expressed with limited or no productive replication.
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.